Is FLNC p.Pro2257= (c.6771A>G) pathogenic?

FLNC p.Pro2257= (c.6771A>G) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.69%, afr); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Pro2257= (c.6771A>G)?

FLNC p.Pro2257= (c.6771A>G) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Pro2257= (c.6771A>G) in the general population?

FLNC p.Pro2257= (c.6771A>G) is low-frequency (popmax 2.69%, afr) (gnomAD).

FLNC p.Pro2257=

c.6771A>G · rs34422412 · VCV129095

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.69%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14
Overall
CADD	0.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.69% African / African-American · 2,015/75,002 alleles

Filtering AF 2.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.55%

Overall 0.168% 2,706/1,609,842 alleles · low-frequency exomes 1,511/1,457,472 · genomes 1,195/152,370 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.69%	37
Admixed American	0.279%	358
Remaining individualsnot grpmax-eligible	0.258%	387
Middle Eastern	0.238%	420
South Asian	0.0355%	2,819
European (non-Finnish)	0.0268%	3,730
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,753

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLNC
Protein: p.Pro2257=
Coding: c.6771A>G
MANE Select: NM_001458
dbSNP: rs34422412
Type: single nucleotide variant
Location: chr7:128854456 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2257: the 'required for interaction with pgm5' region; the 'disordered' region

Full FLNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

Similar variants

FLNC c.1047+1G>T Likely pathogenic ★★ same condition
FLNC c.1048-1G>A Likely pathogenic ★★ same condition
FLNC c.1210+1G>A Likely pathogenic ★★ same condition
FLNC c.1549+2T>G Likely pathogenic ★★ same condition
FLNC c.2007+1G>A Likely pathogenic ★★ same condition
FLNC c.2550+1G>C Likely pathogenic ★★ same condition
FLNC c.2550+2T>C Pathogenic/Likely pathogenic ★★ same condition
FLNC c.2930-1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/flnc-p-pro2257 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown